维生素D代谢基因变异之间的相互作用：与维生素D缺乏症、类风湿性关节炎及其临床疾病活动的关联。

Interaction Between Vitamin D Metabolism Genetic Variants: Association with Hypovitaminosis D, Rheumatoid Arthritis, and Its Clinical Disease Activity.

作者信息

Campos-López Bertha, Rivera-Escoto Melissa, Ruiz-Ballesteros Adolfo I, Pesqueda-Cendejas Karen, Mora-García Paulina E, Meza-Meza Mónica R, Parra-Rojas Isela, Moreno-Ortíz José M, Turiján-Espinoza Eneida, Vargas-Morales Juan M, Cerpa-Cruz Sergio, De la Cruz-Mosso Ulises

机构信息

Red de Inmunonutrición y Genómica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.

Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.

出版信息

Genes (Basel). 2025 Aug 18;16(8):967. doi: 10.3390/genes16080967.

DOI:10.3390/genes16080967

PMID:40870018

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12386013/

Abstract

BACKGROUND

Hypovitaminosis D has been associated with worse rheumatoid arthritis (RA) manifestations. Notably, different genetic studies have reported that approximately 65% of hypovitaminosis D can be partially explained using the presence of single-nucleotide variants (SNVs) in key genes involved in its metabolism. This study aimed to investigate the association and gene-gene interactions of four SNVs in vitamin D metabolism genes, rs10741657 (), rs10877012 (), rs4809959 ), and rs731236 () with hypovitaminosis D, RA, and its clinical disease activity in a Mexican mestizo population.

METHODS

This study was conducted among females: 204 RA patients and 204 control subjects (CS). Vitamin D serum levels (calcidiol) were analyzed using ELISA, SNVs through allelic discrimination with TaqMan probes, and were analyzed using a multifactor dimensionality reduction (MDR) method.

RESULTS

MDR analysis suggested that GG and TT genotypes of rs10877012 () were linked to lower calcidiol levels, while the CT and CC genotypes of rs731236 () were associated with increased RA susceptibility and higher disease activity. Logistic regression confirmed that the GG genotype of rs10877012 () was associated with hypovitaminosis D (OR = 1.8; CI: 1.1-3.0; = 0.01), and the CT genotype of rs731236 () with RA (OR = 1.9; CI: 1.2-2.9; < 0.01) and high DAS28-ESR (OR = 3.6; CI: 1.3-10.7; < 0.01).

CONCLUSIONS

The GG genotype of rs10877012 was associated with susceptibility to hypovitaminosis D, whereas the CT genotype of rs731236 confers susceptibility to RA and high clinical disease activity in the Mexican mestizo population.

摘要

背景

维生素D缺乏与类风湿关节炎（RA）的更严重表现相关。值得注意的是，不同的基因研究报告称，约65%的维生素D缺乏可部分通过参与其代谢的关键基因中存在单核苷酸变异（SNV）来解释。本研究旨在调查墨西哥混血人群中维生素D代谢基因rs10741657（）、rs10877012（）、rs4809959（）和rs731236（）的四个SNV与维生素D缺乏、RA及其临床疾病活动的关联和基因-基因相互作用。

方法

本研究在女性中进行：204例RA患者和204例对照受试者（CS）。使用酶联免疫吸附测定（ELISA）分析血清维生素D水平（骨化二醇），通过TaqMan探针进行等位基因鉴别分析SNV，并使用多因素降维（MDR）方法进行分析。

结果

MDR分析表明，rs10877012（）的GG和TT基因型与较低的骨化二醇水平相关，而rs731236（）的CT和CC基因型与RA易感性增加和较高的疾病活动相关。逻辑回归证实，rs10877012（）的GG基因型与维生素D缺乏相关（比值比[OR]=1.8；置信区间[CI]：1.1 - 3.0；P = 0.01），rs731236（）的CT基因型与RA相关（OR = 1.9；CI：1.2 - 2.9；P < 0.01）以及与高疾病活动评分28-红细胞沉降率（DAS28-ESR）相关（OR = 3.6；CI：1.3 - 10.7；P < 0.01）。